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And Sadelain, M. 2000. The cHS4 insulator increases the probability of retroviral expression at random chromosomal integration sites. J Virol 74: 4679–4687. 60. , Hawley, T. , and Hawley, R. G. 2003. Performance- and safety-enhanced lentiviral vectors containing the human interferon-beta scaffold attachment region and the chicken beta-globin insulator. Blood 101: 4717–4724. 61. , et al. 2007. Extended core sequences from the cHS4 insulator are necessary for protecting retroviral vectors from silencing position effects.

Further investigations showed that even cellular RNAs without any retroviral elements may be packaged to a low extent, a process which was termed retrofection (Linial, 1987; Linial and Miller, 1990). , 1990). The risk arising from the packaging of cellular genes is probably low as their RNAs may not compensate for any viral function and thus could not contribute to the formation of RCRs. indd 22 and are preferentially transmitted. A safety problem arises if these RNAs are able to change the properties of infected cells, as for example the oncogenes do.

Acute myeloid leukemia associated with retroviral gene transfer to hematopoietic progenitor cells of a rhesus macaque. Blood 107: 3865–3867. 18. Cavazzana-Calvo, M. and Fischer, A. 2007. Gene therapy for severe combined immunodeficiency: Are we there yet? J Clin Invest 117: 1456–1465. 19. Moolten, F. L. and Cupples, L. A. 1992. A model for predicting the risk of cancer consequent to retroviral gene therapy. Hum Gene Ther 3: 479–486. 20. , and Galla, M. 2006. Retrovirus vectors: Toward the plentivirus?

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